The data represent sound reference distributions of semen characteristics of fertile men in a number of countries. They provide an appropriate tool in conjunction with clinical data to evaluate a patient's semen quality and prospects for fertility.

In certain cases of infertility in domestic species, and in the homozygous c-ros tyrosine kinase knockout mouse, males are infertile as a result of unopposed sperm swelling. This induces flagellar angulation, preventing their normal migration in the female tract. Angulation always occurs at the site of the cytoplasmic droplet located in mature sperm at the annulus (midpiece - principal piece junction). This article reviews the literature on the fate of the sperm's cytoplasmic droplet and suggests a role for it in volume regulation. A hypothesis is presented that during epididymal transit sperm acquire osmolytes accumulated by the epididymal epithelium. This is possibly driven by a mechanism of regulatory volume increase invoked by the hypertonicity of epididymal luminal fluid. These osmolytes are subsequently used for regulatory volume decrease after ejaculation into the relatively hypotonic female tract. Study of the mechanisms of sperm volume regulation may highlight new contraceptive leads.

The potential of spermatozoa to become motile during post-testicular maturation, and the relationship between the cytoplasmic droplet and fertilizing capacity are reviewed. Post-testicular maturation of spermatozoa involves the autonomous induction of motility, which can occur in vivo in testes with occluded excurrent ducts and in vitro in testicular explants, and artefactual changes in morphology that appear to occur in the testis in vitro. Both modifications may reflect time-dependent oxidation of disulphide bonds of head and tail proteins. Regulatory volume decrease (RVD), which counters sperm swelling at ejaculation, is discussed in relation to loss of cytoplasmic droplets and consequences for fertility. It is postulated that: (i) fertile males possess spermatozoa with sufficient osmolytes to drive RVD at ejaculation, permitting the droplet to round up and pinch off without membrane rupture; and (ii) infertile males possess spermatozoa with insufficient osmolytes so that RVD is inadequate, the droplet swells and the resulting flagellar angulation prevents droplet loss. Droplet retention at ejaculation is a harbinger of infertility caused by failure of the spermatozoon to negotiate the uterotubal junction or mucous and reach the egg. In this hypothesis, the epididymis regulates fertility indirectly by the extent of osmolyte provision to spermatozoa, which influences RVD and therefore droplet loss. Man is an exception, because ejaculated human spermatozoa retain their droplets. This may reflect their short midpiece, approximating head length, permitting a swollen droplet to extend along the entire midpiece; this not only obviates droplet migration and flagellar angulation but also hampers droplet loss. Keywords: epididymis; fertility; infertility; sperm maturation INTRODUCTION During passage of mammalian spermatozoa through the epididymal duct, the functionally incompetent germ cell produced by the testis is matured and stored. In this time (around 1-2 weeks in most species), the spermatozoon undergoes many changes that prepare it for achieving the diverse tasks required of it. At ejaculation, when it is rapidly expelled from the epididymis through the vas deferens to the world outside, the spermatozoon undergoes another phase in which it encounters fluids of the male accessory sex glands, escapes from them in the vagina, cervix or uterus, depending on species, and interacts with the oviductal lining before fertilizing the female gamete. Many mechanisms control the timing of these events, all of which require adequate responses by the fertilizing spermatozoon, and several of these have their origins in the epididymis. This paper addresses a few controversial, novel or still unanswered topics related to the maturation, volume regulation and morphology of spermatozoa.

Homozygous c-ros knockout male mice that lack prepubertal differentiation of the epididymal initial segment are healthy but sterile, despite normal sperm production and mating. Detailed computerized analysis of the motility of spermatozoa maturing in the epididymis revealed only minor defects. However, the majority of motile mature sperm released from the cauda epididymidis showed various extents of flagellar angulation that could not be corrected by raising extracellular osmolality. Measurement of the osmolality of cauda epididymal fluid showed no difference from the wild type. Studies in wild-type mice indicated a maturational change in the ability of motile sperm to maintain straight flagella during incubation, but angulation was induced in cauda sperm by the volume-sensitive ion channel blockers quinine, 5-nitro-2-(3-phenylpropylamino)-benzoic acid and BaCl(2), or by exposure to hypotonic media. Flagellar angulation, induced in the wild type or intrinsic to the knockout, was relieved upon demembranation by Triton X-100, confirming that it was a cell swelling phenomenon. A lack of response of immature wild-type sperm and mature knockout sperm to the channel blockers suggests that there is normally a development of the volume regulatory mechanisms upon maturation that is defective in sperm from the knockout animal. The resultant flagellar angulation may account for the reduction in sperm numbers in the oviduct of mated females and the failure to fertilize in vivo.

No abstract